The term "congenital
hypogonadotropic hypogonadism" (CHH) refers to a group of disorders featuring complete or partial pubertal failure due to insufficient secretion of the
pituitary gonadotropins LH and FSH. Many boys (or their parents) will seek medical consultation because of partial or absent
virilization after 14 yr of age. Small testes are very frequent, but height is generally normal. Laboratory diagnosis of
hypogonadotropic hypogonadism is relatively simple, with very low circulating total
testosterone and low to low-normal
gonadotropin and
inhibin B levels. This
hormone profile rules out a primary testicular disorder. Before diagnosing CHH, however, it is necessary to rule out a
pituitary tumor or pituitary infiltration by imaging studies,
juvenile hemochromatosis, and a systemic disorder that, by undermining nutritional status, could affect
gonadotropin secretion and pubertal development. Anterior pituitary function must be thoroughly investigated to rule out a more complex endocrine disorder with multiple
hormone deficiencies and thus to conclude that the
hypogonadotropic hypogonadism is isolated. The most likely differential diagnosis before age 18 yr is constitutional delay of puberty. Apart from non-Kallmann syndromic forms, which are often diagnosed during childhood, the two main forms of CHH seen by endocrinologists are
Kallmann syndrome, in which CHH is associated with impaired sense of smell, and isolated CHH with normal olfaction.
Anosmia can be easily diagnosed by questioning the patient, whereas olfactometry is necessary to determine reliably whether olfaction is normal or partially defective. This step is important before embarking on a search for genetic mutations, which will also be useful for genetic counseling. The choice of a particular
hormone replacement therapy protocol aimed at virilizing the patient will depend on age at diagnosis and local practices.